There is an urgent need for the development of new drugs or a new application of existing drugs to the treatment of multiple sclerosis and other incurable neurologic disorders. The application of tetracycline derivatives, such as minocycline or doxycycline, to the treatment of multiple sclerosis based on our data is an advance in the treatment of this disease, both as a primary therapy and in support of transplant-induced brain repair.
Multiple sclerosis is an inflammatory disease of the central nervous system (CNS) in which demyelination results in a variety of neurologic deficits. In many patients the disease relapses and remits while in others there is a progressive worsening with no remissions. At present, the only drugs that have been found to be effective in slowing or lessening the disease burden are xcex2-interferon and copolymer-I. However, neither cures the disease and in many patients there is little or no effect. While T-cells are the early inflammatory cells found in areas of demyelination (plaques) in multiple sclerosis patients, microglia in these areas become activated and are thought to produce a number of cytotoxic cytokines. These cytokines are then thought to play a key role in the subsequent demyelination and oligodendrocyte death.
The best available model of multiple sclerosis is EAE (Experimental Allergic Encephalomyelitis). While there are differences between EAE and Multiple Sclerosis, EAE remains as the standard model in which to test therapeutic strategies. Indeed, some Phase I trials in multiple sclerosis patients have been based on experimental therapies of EAE. While EAE can be generated in both rats and mice and by using a number of protocols, we induce the disease in DA (Dark Agouti) rats by the injection of myelin-oligodendrocyte glycoprotein (MOG) in incomplete Freund""s adjuvant. This creates a severe, often relapsing-remitting neurologic disease, like multiple sclerosis, with paralysis of the hind limbs 12-15 days after immunization. Histologically, there is scattered demyelination associated with inflammation and microglial activation.
In one embodiment, the present invention is a method of treating multiple sclerosis comprising the step of treating a multiple sclerosis patient with a tetracycline derivative, wherein the derivative is lipid soluble, and wherein the multiple sclerosis symptoms of the patient are diminished.
In a preferred embodiment, the tetracycline derivative is selected from the group consisting of minocycline and doxycycline and the tetracycline derivative treatment is timed to prevent a relapse of multiple sclerosis symptoms.
In another embodiment of the invention, the treatment is at the time of a triggering event, typically a viral infection.
In another embodiment, the present invention is a method of treating multiple sclerosis patients wherein a multiple sclerosis patient is treated with a tetracycline derivative, wherein the tetracycline derivative is lipid soluble, prior to or at the same time as receiving a transplant of oligodendrocyte progenitor cells to repair chronic areas of the demyelination. Preferably, the tetracycline-derivative is supplied at least three days before transplantation of cells.
It is an object of the present invention to treat the symptoms of multiple sclerosis.
Other objects, features and advantages of the present invention will become apparent after one has examined the specification, claims and drawings.